A prospective, randomized, controlled animal trial.
SETTING: University research laboratory.
SUBJECTS: Anesthetized male Wistar rats, weighing 250 to 350 g.
INTERVENTIONS: MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of
atrial natriuretic peptide,
arginine vasopressin, and
aldosterone were measured, and changes in hemodynamic parameters and renal function were monitored in rats with endotoxic
shock after catheterization of the right jugular vein. Urine volume, urine
sodium excretion, urinary
potassium excretion, and urine 3', 5'-cyclic
guanosine monophosphate (cGMP) excretion were measured at 12-hr intervals. The plasma
atrial natriuretic peptide concentration was slightly but significantly lower 30 mins after the
lipopolysaccharide injection (114.8 +/- 9.0 pg/mL at 0 hr, 75.6 +/- 6.2 pg/mL at 30 mins, p < .01) and then began to increase, peaking at 6 hrs (752.8 +/- 104.5 pg/mL, p < .01 vs. 0 time) and remaining at higher concentrations than before the preinjection value, up to 24 hrs. In contrast, acute spike-like increases of
arginine vasopressin and
aldosterone concentrations were observed 30 mins after the
lipopolysaccharide injection, preceding the increase of the plasma
atrial natriuretic peptide concentration. Measurements of urine volume and urine
sodium excretion showed
oliguria during the initial 12 hrs after the
lipopolysaccharide injection, followed by diuresis and natriuresis during the subsequent 12 hrs. In addition, injection with anti-
atrial natriuretic peptide serum in the
diuretic phase 12 hrs after the
lipopolysaccharide injection significantly inhibited the diuresis, natriuresis, and urine cGMP excretion in this model. Furthermore, the plasma
aldosterone concentration 24 hrs after the
lipopolysaccharide injection was significantly increased by the administration of the
antisera.
CONCLUSIONS: These findings suggest that endogenous
atrial natriuretic peptide increases in the acute phase of endotoxic
shock and plays an important role in water and electrolyte balance by regulating diuresis.